Cogent Biosciences Announces Positive Lead-In Data from Ongoing Phase 3 PEAK Trial Evaluating Bezuclastinib in Combination with Sunitinib in Patients with Gastrointestinal Stromal Tumors (GIST)

-  Data presented at ASCO annual meeting demonstrate 55% Disease Control Rate (DCR) in heavily pre-treated GIST patients, including 100% DCR and 17% overall response rate (ORR) in efficacy evaluable 2^nd-line GIST patients; data immature to estimate progression free survival (PFS)

-  Combination of bezuclastinib and sunitinib is well-tolerated and consistent with published sunitinib monotherapy safety profile

-  Cogent to host investor webcast Monday, June 5 at 8:00 a.m. ET

WALTHAM, Mass. and BOULDER, Colo., June 03, 2023 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced positive lead-in data from its ongoing Phase 3 PEAK trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with Gastrointestinal Stromal Tumors (GIST). The data are being presented today in a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. 

“The results presented today from the lead-in portion of the PEAK study are very encouraging, as the data continue to show that the combination of bezuclastinib and sunitinib has impressive clinical activity in highly refractory GIST patients and is well-tolerated,” said Andrew Wagner, M.D., Ph.D., Senior Physician, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. “These data reinforce the importance of the ongoing Phase 3 PEAK clinical trial, which has the potential to bring a new standard of care to imatinib-resistant GIST patients.”

“These data reinforce our belief that the combination of bezuclastinib and sunitinib has the potential to become a new treatment option for second-line GIST patients,” said Andrew Robbins, President, and Chief Executive Officer at Cogent Biosciences. “We are pleased to demonstrate in a robust clinical dataset that the addition of bezuclastinib to sunitinib does not appear to change the frequency or severity of adverse events associated with sunitinib monotherapy. In addition, we are encouraged by the performance of this combination in second-line GIST patients, the population we are currently enrolling in the Phase 3 PEAK clinical trial, with a disease control rate of 100% and 4 out of 7 patients now on treatment for more than 10 cycles.” 

PEAK Study Design
The PEAK study is a randomized, open-label, global, Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib in GIST patients previously treated with imatinib. As of the data cutoff date of March 29, 2023, 39 patients had been treated in Part 1, with 19 patients in Part 1a and 20 patients in Part 1b. Seven patients had received only imatinib as prior therapy, and 32 patients had received at least 2 prior tyrosine kinase inhibitor (TKI) therapies.

Safety Data 
As of the cutoff date of March 29, 2023, the combination of bezuclastinib and sunitinib was generally well-tolerated with an encouraging safety profile. The majority of treatment-emergent adverse events (TEAEs) were low-grade and reversible, with a low rate of Grade 3 or higher events observed. 23% of patients experienced dose reductions of either medication, and only two patients discontinued treatment due to adverse events. Across Part 1a and Part 1b, there were only two patients with serious adverse events reported that were possibly associated with either study medication including one patient with grade 2 neutrophil count decrease and pyrexia and grade 3 platelet count decrease and one patient with grade 2 bacterial peritonitis and grade 3 febrile neutropenia. Overall, the safety and tolerability profile of the combination appears consistent with that of single-agent sunitinib, suggesting that bezuclastinib is not adding to the overall frequency or severity of adverse events associated with single-agent sunitinib.

Clinical Activity Data 
As of the cutoff date, 39 patients had been treated for at least one 28-day cycle, with a range of 1-13 cycles, and 25 of the 39 patients continue to receive treatment. Data were immature to estimate median progression free survival. Across the efficacy evaluable patients in Part 1, the disease control rate (CR + PR + durable SD) is currently 55%; including a 100% disease control rate and 17% ORR among the efficacy evaluable 2^nd-line patients in Part 1a. Across the study, 21 patients have demonstrated radiographic evidence of reduction in target lesion diameter, including 4 patients who have achieved partial response. Among those responders the time to first response was as long as 8 cycles, suggesting that patients currently early in treatment may achieve responses over time.

As of June 1, 2023 four of the seven 2^nd-line patients in Part 1a remain on study with at least 10 cycles of therapy.

Bezuclastinib Clinical Development 
Cogent is actively enrolling patients in Part 2 of the Phase 3 registration-enabling PEAK trial, which is expected to include approximately 388 second-line, post imatinib GIST patients. Additionally, Cogent remains on track to present initial clinical data from SUMMIT, a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 trial of bezuclastinib in patients with nonadvanced systemic mastocytosis in the second half of 2023. Data will include safety/tolerability, pharmacokinetics, and measures of clinical activity. The Company also expects to present clinical data from approximately 30 patients in Part 1 of the Phase 2 APEX trial in patients with advanced systemic mastocytosis at a scientific meeting in the second half of 2023. 

Webcast Information and ASCO Poster 
Cogent will host a webcast on Monday, June 5, 2023 at 8:00 a.m. ET (7:00 a.m. CT) to discuss today’s update, with participation from Andrew Wagner, M.D., Ph.D., Senior Physician, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. The live event can be accessed on the Investor page of Cogent’s website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days. 

The ASCO poster is available to registered conference attendees and is also in the Posters and Publications section of Cogent’s website at www.cogentbio.com/research. 

About Cogent Biosciences, Inc. 
Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting FGFR2 and ErbB2. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at
www.cogentbio.com. Follow Cogent Biosciences on social media: Twitter and LinkedIn. Information that may be important to investors will be routinely posted on our website and Twitter. 

Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the potential for bezuclastinib to bring a new standard of care to imatinib-resistant GIST patients, the anticipated size of the company’s Phase 3 PEAK trial, the company’s plan to present initial clinical data from SUMMIT in the second half of 2023, and the company’s plan to present clinical data from Part 1 of the APEX trial at a scientific meeting in the second half of 2023. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof.

Contact:
Christi Waarich
Senior Director, Investor Relations
[email protected]
617-830-1653